Empirical solvent-mediated potentials hold for both intra-molecular and inter-molecular inter-residue interactions
Empirical solvent-mediated potentials hold for both intra-molecular and inter-molecular inter-residue interactions
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DOI：
10.1002/pro.5560071211
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发表时间：
1998-12-01
期刊：
影响因子：
8
通讯作者：
Jernigan, RL
中科院分区：
文献类型：
--
作者：
Keskin, O;Bahar, I;Jernigan, RL
在一些研究中，基于知识的分子内残基间电位是否有效地表示发生在蛋白质和蛋白质界面上的分子间相互作用受到了质疑。指出了界面和单链单体之间的链连通性效应和残渣堆积几何形状的差异可能是两种情况下不同能量学的来源。在本研究中，使用与先前采用的分子内残基对相同的统计方法，研究了蛋白质-蛋白质复合物的界面区域以提取分子间残基电位。导出了两组能量参数，分别对应于溶剂介质和“平均残渣”介质。结果表明，前者与单链单体内残基间相互作用的相关性较高（相关系数0.89），后者与分子内残基间相互作用的相关性较弱（0.69）。除了分子内和分子间溶剂介导的电位非常相似外，它们还具有明显的单残基特异性，因此与残基介导的电位相比具有区别性，这表明溶剂介导在控制残基间有效相互作用方面起着重要作用，无论是在界面上还是在单体内。基于这一观察结果，提出了一组包含20个单体项和3个二体项的简化能量参数（与20 × 20残差势表相反），再现了传统的20 × 20表，相关系数为0.99。
Whether knowledge-based intra-molecular inter-residue potentials are valid to represent inter-molecular interactions taking place at protein-protein interfaces has been questioned in several studies. Differences in the chain connectivity effect and in residue packing geometry between interfaces and single chain monomers have been pointed out as possible sources of distinct energetics for the two cases. In the present study, the interfacial regions of protein-protein complexes are examined to extract inter-molecular inter-residue potentials, using the same statistical methods as those previously adopted for intra-molecular residue pairs. Two sets of energy parameters are derived, corresponding to solvent-mediation and "average residue" mediation. The former set is shown to be highly correlated (correlation coefficient 0.89) with that previously obtained for inter-residue interactions within single chain monomers, while the latter exhibits a weaker correlation (0.69) with its intra-molecular counterpart. In addition to the close similarity of intra- and inter-molecular solvent-mediated potentials, they are shown to be significantly mon residue-specific and thereby discriminative compared to the residue-mediated ones, indicating that solvent-mediation plays a major role in controlling the effective inter-residue interactions, either at interfaces, or within single monomers. Based on this observation, a reduced set of energy parameters comprising 20 one-body and 3 two-body terms is proposed (as opposed to the 20 x 20 tables of inter-residue potentials), which reproduces the conventional 20 x 20 tables with a correlation coefficient of 0.99.